Introduction to Biotransformation (Metabolism) - Pesticide Biotransformation and Disposition - page 67

This polymorphism is due to a deletion in the GSTM1 gene resulting in the lack
of GSTM1 protein formation. Epidemiological studies have implicated this deficiency
in an increased risk of lung cancer in smokers, presumably because of the ability of
GSTM1 to detoxify chemical carcinogens such as BaP in tobacco smoke ( Bell et al.,
1992; Nakachi et al., 1993; Seidegard and Pero, 1985; Wormhoudt et al., 1999 ).
Because conjugation reactions other than those mediated by the GSTs are less
well known in the metabolism of pesticides, the enzymatic basis of these conjuga-
tions is not discussed in detail. However, this matter has been reviewed by Motoyama
and Dauterman (1980) , Dorough (1984) , Matsumura (1985) , and Hollingworth et al.
(1995) , and several types of conjugation are known to involve pesticides.
Glucuronyl Transferases
Glucuronidation is one of the most important reactions for the elimination of xeno-
biotics from the body, although not as yet well studied in the case of pesticides or
the phase I metabolites of pesticides. Glucuronidation involves the reaction of uridine
5  -diphosphoglucuronic acid with one of a number of possible functional groups, such
as R-OH, R-NH 2 , R-COOH, and others ( Hodgson and Rose, 2010 ).
Glucuronides are, however, important in the metabolism of carbamates such
as banol, carbaryl, and carbofuran ( Mehendale and Dorough, 1972 ) as well as some
organophosphate compounds ( Hutson, 1981 ) and other chemicals.
Sulfotransferases
Sulfation and sulfate conjugate hydrolysis, catalyzed by various members of the sulfo-
transferases (SULT) and sulfatase enzyme superfamilies, may play a role in the metab-
olism and disposition of many xenobiotics. Reactions of the sulfotransferase enzyme
with various xenobiotics generally result in the production of water-soluble sulfate
esters, which are then eliminated. SULTs, generally speaking, catalyze the sulfation
reaction while the sulfatases catalyze the hydrolysis of the sulfate esters formed by the
action of the SULTs.
Further details of the biochemical and molecular aspects of SULTs can be found in
Hodgson and Rose (2010) .
Other Phase II Enzymes
Methyltransferases
There are a number of enzymatic methyltransferase reactions, including N-, O-, and
S-methylation, and the substrates for these enzymes may be either xenobiotics or
endogenous metabolites. The enzymes involved are briefly described in Hodgson
(2010) . For almost all methylation reactions the methyl donor is S -adenosylmethionine,
formed from methionine and ATP.